Chemical and/or pharmaceutical processes can be controlled efficiently only if the current composition of the substance mixture and the respective properties of the individual substances of the substance mixture can be determined with sufficient accuracy in the various process steps.
The methods for the said determination of the aforementioned composition, or the aforementioned properties of the substances, include spectroscopic measurement methods.
If such spectroscopic measurement methods are used with suitable apparatuses directly in chemical and/or pharmaceutical processes, they are referred to as online spectroscopic measurement methods.
Such online spectroscopic measurement methods allow direct continuous monitoring of a running chemical and/or pharmaceutical process.
The aforementioned apparatuses suitable for online spectroscopic measurement methods include optical probes.
Online spectroscopic measurement methods are of particular importance since usually no intervention in the chemical and/or pharmaceutical process is carried out by the measurement method.
That is to say, neither the quantitative flow of the substances nor the composition of the substance mixture or the chemical nature of the substances is altered by the measurement. The latter, however, applies only when the substances of the substance mixture to be measured are chemically stable under the effect of electromagnetic radiation (usually in the form of light) which is introduced in small amounts into the process by the analysis. Yet since the amount of electromagnetic radiation required for online spectroscopic measurement methods is usually very small, this problem arises only in negligibly few cases.
Thus, if the online spectroscopic measurement method involves no intervention in the chemical and/or pharmaceutical process, the method is referred to as a noninvasive method, and here in particular a noninvasive online spectroscopic measurement method.
The aforementioned noninvasive online spectroscopic measurement methods therefore offer the combined advantages that direct sample contact of the measurement position, and therefore direct measurement value acquisition, is possible, but at the same time no sampling, preparation or other intervention needs to be carried out in the chemical and/or pharmaceutical process.
As explained above, noninvasive online spectroscopic measurement methods offer the advantage of the possibility of direct sample contact with the measurement position and therefore the possibility of direct measurement value acquisition in the running process. So that this general advantage can be fully exploited, as explained above a suitable measuring apparatus must be available.
Such suitable measuring apparatuses for noninvasive online spectroscopic measurement methods are so-called optical probes, which include the reflection probe according to the present invention.
In this context, “suitable” means in particular that the optical probe has at all times direct optical access to the substance or substance mixture to be studied.
Pharmaceutical and chemical processes are usually carried out in closed apparatuses and/or pipelines. These are generally opaque for the wavelength range which is used for the analysis.
In the said apparatuses and/or pipelines, it is therefore usually necessary to provide windows which are transparent for the wavelength range used, in order to make it possible to monitor the processes in the reactor space or the connected pipelines.
In certain applications, however, such simple windows, albeit ones which are often encountered in chemical and/or pharmaceutical processes, have significant disadvantages.
For instance, in many chemical and/or pharmaceutical processes the substances and/or substance mixtures have adhesive properties and/or are very viscous. That is to say, in running operation of the chemical and/or pharmaceutical process it happens that at least some of the substance mixtures adheres permanently on the window surface and remains there. Consequently, a noninvasive online spectroscopic measurement carried out on the window will be defective because substantially the same substance mixture, which probably does not correspond in its composition to the rest of the substance mixture which is not adhering, will constantly be analysed.
Substances and/or substance mixtures which lead to the said adhesions on such windows are in particular—to mention only two—suspensions and emulsions.
The aforementioned disadvantages give rise to the essential requirement of configuring the measuring apparatus—the probe—in such a way that operating states in which adhesions as mentioned above occur can be immediately detected, so that these can be removed and/or excluded.
In particular for use of such a measuring apparatus—probe—in pharmaceutical processes, particular requirements are to be satisfied in respect of the material quality and/or surface of the measuring apparatus, and in particular the geometry of the measuring apparatus should be configured in such a way that such adhesions either do not occur or can be fully removed from the site of the measurement.
For the input or output of electromagnetic radiation into or from the measurement position (i.e. the site for the measuring apparatus in the reactor, or in the pipeline), so called coupling lines are often used. For this reason, coupling of the electromagnetic radiation in and out is also referred to in this context.
Such coupling lines are flexible lines which make it possible to transmit electromagnetic radiation over a certain path, without accurate positioning of the optical components along this path being necessary.
Above all, glass fibre cables from the telecommunications sector are known. In connection with the measurement methods and measuring apparatuses in question here for chemical and/or pharmaceutical processes, so-called waveguide couplings or special silver halide or fluoride glass light guides are conventionally used.
The aforementioned waveguide couplings or special silver halide or fluoride glass light guides are usually suitable for the guiding of electromagnetic radiation in the mid-infrared range (400-4000 cm−1).
In the near infrared range (NIR: 4000-14000 cm−1) and ultraviolet/visible range (UV/Vis: 200-700 nm), it is usual to use quartz light guides which have a particularly low attenuation in these spectral ranges.
The use of such light guides is described, for example, in DE 20 2009 002065. These guide electromagnetic radiation in the form of light, emitted by a pulsed laser with an energy of 20 W per pulse, into a measuring apparatus which introduces the light into the measurement space through a sapphire glass window. The light passes through the measurement space and enters the measuring apparatus—probe—again through a further sapphire glass window, whereupon the remaining light is conveyed to an optical detector through a further light guide.
The apparatus in each configuration described in DE 20 2009 002065 is a transmission measuring apparatus. That is to say, with the aforementioned detector a measurement value is acquired which, by means of suitable calibration, makes it possible to deduce the composition of the medium present in the measurement space from the extinction of this medium. In the case of DE 20 2009 002065, the medium is milk, the fat content of which is intended to be determined.
According to DE 20 2009 002065, sapphire windows are employed because they are resistant to the abrasive media used to clean the measurement space. It follows from this that the apparatus according to DE 20 2009 002065 has the disadvantage that it cannot be operated continuously without deposits at the site of the measurement. DE 20 2009 002065 does not disclose any possibilities for keeping the site of the measurement free from, or ridding it of, deposits during running operation.
As is known, milk is an emulsion of fat in water, so that DE 20 2009 002065 reinforces in particular the existing problems of online spectroscopic measurement methods in respect of adhesions. According to the description of DE 20 2009 002065, a transmission measurement method is used because the accuracy of a reflective measurement method using a reflection probe would be insufficient. According to the indications in DE 20 2009 002065, the nature and exact origin of the reflections is not yet in fact fully understood physically.
WO 2007/098003 describes such a reflective measurement method, and a measuring apparatus—probe—suitable for such a reflective measurement method.
WO 2007/098003 also deals implicitly with the problem of a malfunction of the measuring apparatus. According to WO 2007/098003, the measuring apparatus—probe—described therein is intended, particularly under the demanding conditions of polymer extrusion, to be useable and replaceable in essential parts as well as recalibratable, without the polymer extrusion process having to be stopped therefor.
According to WO 2007/098003, this problem is resolved in that a unit comprising an optical window is connected firmly by a screw-in device to the apparatus/pipeline in which measurement is to be carried out, the optical window in turn being closed in a leaktight fashion relative to the measurement space by means of a further screw-in device. As a consequence of this, the further measuring arrangement located behind the unit comprising the optical window can be replaced without requiring an intervention in the method.
However, the measuring apparatus according to WO 2007/098003 also does not prevent polymer from adhering to the optical window, or provide devices which could remove such polymer without interrupting the polymer extrusion process.
A feature common to the two measuring apparatuses—probes—described above for noninvasive online spectroscopic measurement is thus the fact that they do not comprise devices which make it possible to keep the site of the measurement free from adhesions without interrupting the chemical and/or pharmaceutical process in question. Therefore, none of the aforementioned measuring apparatuses—probes—can represent continuously correct measurement operation for noninvasive online spectroscopic measurement without interruption of the chemical and/or pharmaceutical process in question.
From the prior art, it is therefore likewise known that besides the measuring apparatus—probe—a suitable cleaning device is applied which makes it possible to clean the measurement position even during operation of the chemical and/or pharmaceutical process, without the latter having to be interrupted therefor. However, this is to be installed in addition to the noninvasive online spectroscopic measuring apparatus, and per se constitutes a further site at which adhesions may form.
As an alternative, measuring apparatuses—probes—of the general type are also known which already have such a cleaning device integrated. Such measuring apparatuses—probes—known from the prior art are, however, usually constructed in such a way that they are installed beside the measurement position in an enlarged holding device, as described for instance in WO 2007/098003.
In the prior art, however, such measuring apparatuses—probes—with an integrated cleaning device are configured in such a way that the cleaning device is raised relative to the measurement position, in order to send a directional flushing jet onto the measurement position.
The effect of this is that they cannot be used in existing equipment comprising moving devices, in particular scraping the inner wall, since in this way at least the cleaning device would come in contact because of the moving parts, such as blades or stirrers. In the least problematic case, this leads to the cleaning device being damaged; in the worst case, the cleaning device blocks the moving parts.
For use in pharmaceutical production, such designs prove to be uncleanable, or poorly cleanable, if only because of the aforementioned raised nature and the further edges and recesses resulting therefrom, and are often not integratable into such processes.